The mean age at onset of HD is around 37 years old, but ranges between two
and 85, with some cases falling outside this range. In individual cases,
disease onset may be difficult to pinpoint, particularly when behavioral
and psychiatric changes are considered. In patients who are closely followed,
a zone of onset appears spanning three to five years. The presenting symptoms
vary. In a review of the nature of onset in 510 HD patients, Di Maio et al.
found that neurological symptoms heralded the disease onset in 59 percent
of subjects, while psychiatric symptoms were first noted in 23 percent, and
18 percent had both at onset.[1]

Studies of motor onset in the Lake Maracaibo,
Venezuela community in which HD is endemic, showed that patients first develop
subtle changes in volitional
eye movement and clumsiness before they show frank motor changes due to the
disease. Initially, people with HD exhibit involuntary, spasmodic movements
of limbs and facial muscles. Over the course of years, they lose normal motor
functions and become bed bound.[2] This is indicative of most patients with
HD.

Juvenile HD, which has a strikingly different phenotype, begins with akinesia,
rigidity and dystonia and is often accompanied by myoclonic muscle tremors
and twitches or seizures. The progression of HD occurs independent of any
therapeutic intervention. It remains unclear whether or not progression
rate relates to
the CAG repeat length, thus limiting the prognostic value of genetic testing
for disease severity and progression.[3,4,5]

Geographic region

Prevalence

Grampian/NE Corner of Scotland (Simpson, 1989)

9.94/100,000

Ireland (Morrison, 1995)

6.4/100,000

New South Wales (McCusker, 2000)

6.3/100,000

Glasgow/West of Scotland (Bolt, 1970)

5.2/100,000

Mauritius, Independent Island Republic in the Western Indian Ocean (Hayden,
1981)

4.6/100,000

Hong Kong (Chang, 1994)

3.7/1,000,000

South Africa (Hayden, 1980)

0.0/1,000,000

The prevalence of HD is estimated to be between three and 10 people/100,000
people of European descent.[6,7] Most patients are identified by the presence
of a suggestive neurologic course in a patient with a positive family history.
However, in a study of symptomatic
patients undergoing confirmatory genetic tests in British Columbia, nearly
25 percent had negative family histories. Although in many cases the family
history is obscured by misdiagnosis, obfuscation or competitive mortality,
researchers estimate that as many as 8 percent of HD patients with negative
family histories may reflect new genetic mutations arising from borderline
premutations. Moreover, the study of HD likely suffers from under reporting
of patients. Studies of mutational flow suggest that accurate diagnosis is
poor with late onset HD. Current epidemiologic data show that there are 25,000
to 30,000 HD patients in the United States. On average, five first-degree relatives
are at risk for each affected person.

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